Contribution of tenosynovitis of small joints to the symptom morning stiffness in patients presenting with undifferentiated and rheumatoid arthritis

Objective: Morning stiffness (MS) is characteristic of rheumatoid arthritis (RA). Despite its association with functional disability, the extent to which local inflammatory processes contribute to this symptom is unknown. Magnetic resonance imaging (MRI)-detected tenosynovitis of small joints is recognized as an early feature of RA, which is also associated with functional impairments. It has been proposed that tenosynovitis contributes to MS. Therefore, we assessed the relationship between MS and MRI-detected inflammation, in particular tenosynovitis. Method: In total, 286 consecutive patients newly presenting with undifferentiated arthritis and RA underwent contrast-enhanced 1.5 T MRI of (2–5) metacarpophalangeal, wrist, and (1–5) metatarsophalangeal joints. Scans were scored for tenosynovitis according to Haavardsholm, and for synovitis by Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS). MS was dichotomized as ≥ 60 min or not. Associations between MS and tenosynovitis/synovitis were tested with logistic regression, data were categorized (solitary or simultaneous presence of synovitis/tenosynovitis), and the presence of an additive interaction was assessed. Results: MS was present in 40% of patients. Tenosynovitis was more often present in patients with MS than without MS [80% vs 65%, odds ratio (OR) 2.11, 95% confidence interval (1.21;3.69)]. Synovitis was more often present in patients with MS [58% vs 44%, OR 1.79 (1.11;2.91)]. In categorized analyses, concurrent synovitis and tenosynovitis had the largest association [OR 2.43 (1.30;4.54)], in contrast to solitary synovitis [OR 0.85 (0.21;3.47)]. The additive interaction was non-significant. The variance explained in all analyses was small (range 4–5%). Conclusion: Tenosynovitis, combined with synovitis, at small joints is associated with MS and contributes to the pathophysiology of MS

Grip strength reduction in clinically suspect arthralgia: natural trajectories and improvement after treatment

Pathophysiology and treatment of rheumatic disease

Enhanced treatment strategies and distinct disease outcomes among autoantibody-positive and -negative rheumatoid arthritis patients over 25 years: a longitudinal cohort study in the Netherlands

Background Based on different genetic and environmental risk factors and histology, it has been proposed that rheumatoid arthritis (RA) consists of 2 types: autoantibody-positive and autoantibody-negative RA. However, until now, this remained hypothetical. To assess this hypothesis, we studied whether the long-term outcomes differed for these 2 groups of RA patients. Methods and findings In the Leiden Early Arthritis Clinic cohort, 1,285 consecutive RA patients were included between 1993 and 2016 and followed yearly. Treatment protocols in routine care improved over time, irrespective of autoantibody status, and 5 inclusion periods were used as instrumental variables: 1993-1996, delayed mild disease-modifying antirheumatic drug (DMARD) initiation (reference period); 1997-2000, early mild DMARDs; 2001-2005, early methotrexate; 2006-2010, early methotrexate followed by treat-to-target adjustments; 2011-2016, similar to 2006-2010 plus additional efforts for very early referral. Three long-term outcomes were studied: sustained DMARD-free remission (SDFR) (persistent absence of clinical synovitis after DMARD cessation), mortality, and functional disability measured by yearly Health Assessment Questionnaire (HAQ). Treatment response in the short term (disease activity) was measured by Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR). Linear mixed models and Cox regression were used, stratified for autoantibody positivity, defined as IgG anti-CCP2 and/or IgM rheumatoid factor positivity. In total, 823 patients had autoantibody-positive RA (mean age 55 years, 67% female); 462 patients had autoantibody-negative RA (age 60 years, 64% female). Age, gender, and percentage of autoantibody-positive patients were stable throughout the inclusion periods. Disease activity significantly decreased over time within both groups. SDFR rates increased after introduction of treat-to-target (hazard ratio [HR] 2006-2010 relative to 1993-1996: 3.35 [95% CI 1.46 to 7.72;p =0.004]; HR 2011-2016: 4.57 [95% CI 1.80 to 11.6;p =0.001]) in autoantibody-positive RA, but not in autoantibody-negative RA. In autoantibody-positive RA, mortality decreased significantly after the introduction of treat-to-target treatment adjustments (HR 2006-2010: 0.56 [95% CI 0.34 to 0.92;p =0.023]; HR 2011-2016: 0.33 [95% CI 0.14 to 0.77;p =0.010]), but not in autoantibody-negative RA (HR 2006-2010: 0.79 [95% CI 0.40 to 1.56;p =0.50]; HR 2011-2016: 0.36 [95% CI 0.10 to 1.34;p =0.13]). Similarly, functional disability improved in autoantibody-positive RA for the periods after 2000 relative to 1993-1996 (range -0.16 [95% CI -0.29 to -0.03;p =0.043] to -0.32 [95% CI -0.44 to -0.20;p <0.001] units of improvement), but not in autoantibody-negative RA (range 0.10 [95% CI -0.12 to 0.31;p =0.38] to -0.13 [95% CI -0.34 to 0.07;p =0.20] units of improvement). Limitations to note were that treatment was not randomized-but it was protocolized and instrumental variable analysis was used to obtain comparable groups-and that a limited spread of ethnicities was included. Conclusions Although disease activity has improved in both autoantibody-positive and autoantibody-negative RA in recent decades, the response in long-term outcomes differed. We propose that it is time to subdivide RA into autoantibody-positive RA (type 1) and autoantibody-negative RA (type 2), in the hope that this leads to stratified treatment in RA.Author summaryWhy was this study done? Patients with rheumatoid arthritis (RA) have different risk factors and histology (microscopic anatomy) depending on the presence or absence of autoantibodies (anti-citrullinated protein antibodies and rheumatoid factor). Because it is suspected that RA with and without autoantibodies are 2 distinct diseases with different pathophysiology, we hypothesized that these 2 types of RA will have reacted differently to improvements in treatment strategies that have taken place over the last decades. What did the researchers do and find? Since its start in 1993, the inclusion criteria of the Leiden Early Arthritis Clinic cohort have not changed, and included RA patients have remained similar, apart from earlier diagnosis; therefore, RA patients from different years were comparable. Treatment protocols enhanced over time, but were similar for patients with and without autoantibodies. We studied the changes in disease activity and 3 long-term outcomes of RA patients with and without autoantibodies over time (inclusion period was a proxy for treatment strategy). We found that while disease activity improved in both patient groups, the long-term outcomes (the possibility to permanently stop medication, mortality, and functional disability) only improved in RA patients with autoantibodies. What do these findings mean? The disconnection between improvement in disease activity and subsequent improvement in long-term outcomes in RA without autoantibodies suggests that the underlying pathogenesis of RA with and without autoantibodies is different. We propose that it is time to formally subdivide RA into type 1 (with autoantibodies) and type 2 (without autoantibodies).Pathophysiology and treatment of rheumatic disease

Early intensive treatment normalises excess mortality in ACPA-negative RA but not in ACPA-positive RA

Pathophysiology and treatment of rheumatic disease

Sensory processing deficiencies in patients with borderline personality disorder who experience auditory verbal hallucinations

Auditory verbal hallucinations (AVH) are common in patients with borderline personality disorder (BPD). We examined two candidate mechanisms of AVH in patients with BPD, suggested to underlie sensory processing systems that contribute to psychotic symptoms in patients with schizophrenia; sensory gating (P50 ratio and P50 difference) and change detection (mismatch negativity; MMN). Via electroencephalographic recordings P50 amplitude, P50 ratio, P50 difference and MMN amplitude were compared between 23 borderline patients with and 25 without AVH, and 26 healthy controls. Borderline patients with AVH had a significantly lower P50 difference compared with healthy controls, whereas no difference was found between borderline patients without AVH and healthy controls. The groups did not differ on MMN amplitude. The impaired sensory gating in patients with borderline personality disorder who experience AVH implies that P50 sensory gating deficiencies may underlie psychotic vulnerability in this specific patient group. Patients with borderline personality disorder with or without AVH did not have problems with auditory change detection. This may explain why they are spared from the poor outcome associated with negative symptoms and symptoms of disorganization in patients with chronic schizophrenia

FeP Nanocatalyst with Preferential [010] Orientation Boosts the Hydrogen Evolution Reaction in Polymer-Electrolyte Membrane Electrolyzer

The development of nonprecious metal electrocatalysts for polymer-electrolyte membrane (PEM) water electrolysis is a milestone for the technology, which currently relies on rare and expensive platinum-group metals. Half-cell measurements have shown iron phosphide materials to be promising alternative hydrogen evolution electrocatalysts, but their realistic performance in flow-through devices remains unexplored. To fill this gap, we report herein the activity and durability of FeP nanocatalyst under application-relevant conditions. Our facile synthesis route proceeds via impregnation of an iron complex on conductive carbon support followed by phosphorization, giving rise to highly crystalline nanoparticles with predominantly exposed [010] facets, which accounts for the high electrocatalytic activity. The performance of FeP gas diffusion electrodes toward hydrogen evolution was examined under application-relevant conditions in a single cell PEM water electrolysis at 22 °C. The FeP cathode exhibited a current density of 0.2 A cm–2 at 2.06 V, corresponding to a difference of merely 0.07 W cm–2 in power input as compared to state-of-the-art Pt cathode, while outperforming other nonprecious cathodes operated at similar temperature. Quantitative product analysis of our PEM device excluded the presence of side reactions and provided strong experimental evidence that our cell operates with 84–100% Faradaic efficiencies and with 4.1 kWh Nm–3 energy consumption. The FeP cathodes exhibited stable performance of over 100 h at constant operation, while their suitability with the intermittency of renewable sources was demonstrated upon 36 h operation at variable power inputs. Overall, the performance as well as our preliminary cost analysis reveal the high potential of FeP for practical applications.</p

Consequences of electron-density manipulations on the X-ray photoelectron spectroscopic properties of ferrocenyl-β-diketonato complexes of manganese(III). structure of [Mn(FcCOCHCOCH3)3]

Reaction of [Mn3(OAc)6O·3H2O](+) (1) with ferrocenyl β-diketones of the type FcCOCH2COR with R = CF3 (2a) and CH3 (2b), Ph = C6H5 (2c), and Fc = Fe(II)(η(5)-C5H4)(η(5)-C5H5) (2d) yielded a series of ferrocene-functionalized β-diketonato manganese(III) complexes 3a-3d, respectively, of general formula [Mn(FcCOCHCOR)3]. The mixed-ligand β-diketonato complex [Mn(FcCOCHCOFc)2(FcCOCHCOCH3)] (4) was obtained by reacting mixtures of diketones 2b and 2d with 1. A single-crystal X-ray structure determination of 3b (Z = 2, triclinic, space group P1̅) highlighted a weak axial elongating Jahn-Teller effect and a high degree of bond conjugation. An X-ray photoelectron spectroscopic study, by virtue of linear relationships between group electronegativities of ligand R groups, χR, or ∑χR, and binding energies of both the Fe 2p3/2 and Mn 2p3/2 photoelectron lines, confirmed communication between molecular fragments of 2a-2d as well as 3a-3d. This unprecedented observation allows prediction of binding energies from known β-diketonato side group χR values.J.C.S. acknowledges the NRF (Grant 2054243) and the UFS for financial support. Financial support from Syngaschem BV, The Netherlands, and the UFS is also gratefully acknowledged (B.E.B., E.E., and J.C.S.).http://pubs.rsc.org/en/journals/journalissues/ic2017-03-31hb2016Chemistr

Handwork vs machine: a comparison of rheumatoid arthritis patient populations as identified from EHR free-text by diagnosis extraction through machine-learning or traditional criteria-based chart review

Background Electronic health records (EHRs) offer a wealth of observational data. Machine-learning (ML) methods are efficient at data extraction, capable of processing the information-rich free-text physician notes in EHRs. The clinical diagnosis contained therein represents physician expert opinion and is more consistently recorded than classification criteria components. Objectives To investigate the overlap and differences between rheumatoid arthritis patients as identified either from EHR free-text through the extraction of the rheumatologist diagnosis using machine-learning (ML) or through manual chart-review applying the 1987 and 2010 RA classification criteria. Methods Since EHR initiation, 17,662 patients have visited the Leiden rheumatology outpatient clinic. For ML, we used a support vector machine (SVM) model to identify those who were diagnosed with RA by their rheumatologist. We trained and validated the model on a random selection of 2000 patients, balancing PPV and sensitivity to define a cutoff, and assessed performance on a separate 1000 patients. We then deployed the model on our entire patient selection (including the 3000). Of those, 1127 patients had both a 1987 and 2010 EULAR/ACR criteria status at 1 year after inclusion into the local prospective arthritis cohort. In these 1127 patients, we compared the patient characteristics of RA cases identified with ML and those fulfilling the classification criteria. Results The ML model performed very well in the independent test set (sensitivity=0.85, specificity=0.99, PPV=0.86, NPV=0.99). In our selection of patients with both EHR and classification information, 373 were recognized as RA by ML and 357 and 426 fulfilled the 1987 or 2010 criteria, respectively. Eighty percent of the ML-identified cases fulfilled at least one of the criteria sets. Both demographic and clinical parameters did not differ between the ML extracted cases and those identified with EULAR/ACR classification criteria. Conclusions With ML methods, we enable fast patient extraction from the huge EHR resource. Our ML algorithm accurately identifies patients diagnosed with RA by their rheumatologist. This resulting group of RA patients had a strong overlap with patients identified using the 1987 or 2010 classification criteria and the baseline (disease) characteristics were comparable. ML-assisted case labeling enables high-throughput creation of inclusive patient selections for research purposes.Pathophysiology and treatment of rheumatic disease